Preliminary Study On The Relationship Between Peripheral Blood Vitamin B12 Level And Gut Microbiota In Pregnant Women With Gestational Diabetes Mellitus

Objective:The global incidence of gestational diabetes mellitus(GDM)is increasing,which is seriously harmful to maternal and infant health.At present,the etiology and pathogenesis of gestational diabetes have not been fully clarified,and the key diagnostic markers for evaluating the progress of gestational diabetes are still lacking.Recent studies have found that the level of trace elements in pregnant women is closely related to the occurrence and development of gestational diabetes,especially the lack of vitamin B12 in peripheral blood.However,there are still few research data on the relationship between vitamin B12 levels and GDM.The purpose of this study is to further reveal the biomarkers related to the occurrence and development of GDM by analyzing the characteristics of serum vitamin B12,serological indexes(folic acid,blood glucose,blood lipids,etc.),inflammatory factors and intestinal flora in patients with GDM in the third trimester of pregnancy,so as to give better guidance to GDM patients in prevention and treatment.Methods:A total of 30 pregnant women in the third trimester of pregnancy were included,including13 in GDM group and 17 in normal glucose tolerance group.Feces and peripheral blood samples of pregnant women were collected.Based on the Hi Seq Sequencing System,the V4 region of16 Sr DNA were analyzed.The sequencing results were analyzed by bioinformatics.Vitamin B12,folic acid,homocysteine,related glycolipid metabolism indexes and inflammatory factors in peripheral blood were detected,and the results were analyzed by SPSS 26.0 statistical software.Spearman correlation analysis was used to reveal the internal relationship among dominant bacteria,vitamin B12,related serological indexes and inflammatory factors.Results:1.Comparison of the basic characteristics of the subjects,there was no significant difference in age,gestational age,blood pressure,BMI,amniotic fluid volume and neonatal weight between the GDM group and the normal group(P>0.05).2.Serological test results: Compared with the normal group,the levels of serum vitamin B12 in GDM group were significantly lower(P < 0.05),FA,TC,FBG,INS,Hb A1c(%),HOMA-IR,pro-inflammatory cytokines(IL-6,TNF-α),anti-inflammatory factors(IL-10)and transcription factor-κB(NF-κB)were significantly higher(P < 0.05).In addition,the level of peripheral blood HCY in GDM group was higher than that in normal group,but the difference was not statistically significant(P = 0.12).3.The results of Pearson correlation analysis between the level of vitamin B12 in peripheral blood and the basic characteristics of the subjects and related serological indexes showed that there was a significant negative correlation between vitamin B12 and amniotic fluid volume,FA,FBG,Hb A1c(%),HOMA-IR,IL-6,TNF-α,IL-10 and NF-κB in pregnant women in the third trimester of pregnancy.4.Intestinal flora 16 Sr DNA sequencing results: Comparing the abundance of intestinal bacteria between the GDM group and the normal group,the top 10 abundance key species were selected at the level of phylum,genus and species respectively,and there was no significant difference(P > 0.05);PCo A analysis based on the Unweighted Uni Frac distance matrix to evaluate the β diversity of the intestinal bacteria of pregnant women in the GDM group and the normal group,which found that the two groups of microbial community composition are significantly different(P = 0.038);the LEfse method was used to further search for the differential bacteria between groups,and found that it was at the genus level Acidaminococcus was significantly enriched in GDM group.5.The results of Spearman correlation analysis between dominant bacteria Acidaminococcus and clinical indexes: there was significant negative correlation between Acidaminococcus and vitamin B12,and significant positive correlation with FA,FBG,INS,HOMA-IR,Hb A1c(%)and NF-κB.There was no statistical correlation between Acidaminococcus and lipid metabolism,pro-inflammatory factors(IL-6,TNF-α)and anti-inflammatory factors(IL-10).Conclusions:1.Vitamin B12 level is relatively low in GDM population in late pregnancy,and the composition of intestinal bacteria will change.Acidaminococcus is the dominant bacteria in the third trimester GDM population,and this bacteria is significantly related to trace elements(B12,FA)and glucose metabolism disorders.2.The level of serum vitamin B12 affects glucose metabolism,the expression of inflammatory factors and the composition of intestinal microorganisms.Vitamin B12 may be closely related to the occurrence and development of GDM and can be used as a potential biomarker to evaluate the condition of GDM in the third trimester of pregnancy.